Gene Symbol: ligA
Description: DNA ligase, NAD(+)-dependent
Alias: ECK2406, JW2403, dnaL, lig, lop, pdeC
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. Panasenko S, Cameron J, Davis R, Lehman I. Five hundredfold overproduction of DNA ligase after induction of a hybrid lambda lysogen constructed in vitro. Science. 1977;196:188-9 pubmed
    A lambda vector that contains the gene for Escherichia coli DNA ligase (lambdagt4-lop-11 lig+) has been modified to achieve overproduction of this enzyme...
  2. Ghelardini P, Liebart J, Paolozzi L, Pedrini A. Suppression of the thermosensitive DNA ligase mutations in Escherichia coli K12 through modulation of gene expression induced by phage Mu. Mol Gen Genet. 1989;216:31-6 pubmed
    ..mutant shows: (i) an increment in the host DNA ligase activity; (ii) an increase in the specific mRNA of the host lig gene; (iii) an increase (towards the relaxed state) in the average linking number of a resident plasmid; and (iv) a ..
  3. Hayashi K, Nakazawa M, Ishizaki Y, Hiraoka N, Obayashi A. Stimulation of intermolecular ligation with E. coli DNA ligase by high concentrations of monovalent cations in polyethylene glycol solutions. Nucleic Acids Res. 1985;13:7979-92 pubmed
    ..The extent of such intermolecular ligation increased and the salt concentrations at which ligation was stimulated extended to lower concentrations when we raised the temperature from 10 to 37 degrees C. ..
  4. Sriskanda V, Shuman S. Conserved residues in domain Ia are required for the reaction of Escherichia coli DNA ligase with NAD+. J Biol Chem. 2002;277:9695-700 pubmed
    ..Here we show that reactivity of Escherichia coli DNA ligase (LigA) with NAD(+) requires N-terminal domain Ia, which is unique to, and conserved among, NAD(+) ligases but absent from ..
  5. Liu L, Tang Z, Wang K, Tan W, Li J, Guo Q, et al. Using molecular beacon to monitor activity of E. coli DNA ligase. Analyst. 2005;130:350-7 pubmed
    ..coli DNA ligase is performed with a broad linear range of 4.0 x 10(-4) Weiss Unit mL(-1) to 0.4 Weiss Unit mL(-1) and the detection limit of 4.0 x 10(-4) Weiss Unit mL(-1). ..
  6. Morse L, Beck L, Pauling C. Effect of chloramphenicol and the recB gene product on DNA metabolism in Escherichia coli K12 strains defective in DNA ligase. Mol Gen Genet. 1976;147:79-82 pubmed
    We have examined DNA strand breakage, DNA degradation, and the rate of DNA synthesis in lig and lig-recB strains of Escherichia coli K12 incubated in the presence and absence of 3 mug/ml chloramphenicol...
  7. Modorich P, Lehman I. Deoxyribonucleic acid ligase. A steady state kinetic analysis of the reaction catalyzed by the enzyme from Escherichia coli. J Biol Chem. 1973;248:7502-11 pubmed
  8. Miesel L, Kravec C, Xin A, McMonagle P, Ma S, Pichardo J, et al. A high-throughput assay for the adenylation reaction of bacterial DNA ligase. Anal Biochem. 2007;366:9-17 pubmed
    ..Certain adenosine analogs were found to inhibit the adenylation assay and had similar potency of inhibition in a DNA ligation assay. ..
  9. Zimmerman S, Little J, Oshinsky C, Gellert M. Enzymatic joining of DNA strands: a novel reaction of diphosphopyridine nucleotide. Proc Natl Acad Sci U S A. 1967;57:1841-8 pubmed

More Information


  1. Sevastopoulos C, Wehr C, Glaser D. Large-scale automated isolation of Escherichia coli mutants with thermosensitive DNA replication. Proc Natl Acad Sci U S A. 1977;74:3485-9 pubmed
    ..Some of the mutants exhibited mutator activity at partially restrictive temperatures. It is argued that some genes involved in DNA synthesis remain to be discovered. ..
  2. Hale C, de Boer P. Direct binding of FtsZ to ZipA, an essential component of the septal ring structure that mediates cell division in E. coli. Cell. 1997;88:175-85 pubmed
    ..ZipA is an essential component of the division machinery, and, by binding to both FtsZ and the cytoplasmic membrane, is likely to be directly involved in the assembly and/or function of the FtsZ ring. ..
  3. Brun Y, Lapointe J. Locations of genes in the 52-minute region on the physical map of Escherichia coli K-12. J Bacteriol. 1990;172:4746-7 pubmed
  4. Sung J, Mosbaugh D. Escherichia coli uracil- and ethenocytosine-initiated base excision DNA repair: rate-limiting step and patch size distribution. Biochemistry. 2003;42:4613-25 pubmed
    ..This BER process was dependent upon DNA polymerase I since very-long patch BER was inhibited by DNA polymerase I antibody and addition of excess DNA polymerase I reversed this inhibition. ..
  5. Wang L, Nair P, Shuman S. Structure-guided mutational analysis of the OB, HhH, and BRCT domains of Escherichia coli DNA ligase. J Biol Chem. 2008;283:23343-52 pubmed publisher
    NAD(+)-dependent DNA ligases (LigAs) are ubiquitous in bacteria and essential for growth. LigA enzymes have a modular structure in which a central catalytic core composed of nucleotidyltransferase and oligonucleotide-binding (OB) domains ..
  6. Dermody J, Robinson G, Sternglanz R. Conditional-lethal deoxyribonucleic acid ligase mutant of Escherichia coli. J Bacteriol. 1979;139:701-4 pubmed
    ..This suggests that the mutant may be among the most ligase-deficient strains yet characterized. ..
  7. Ciarrocchi G, Macphee D, Deady L, Tilley L. Specific inhibition of the eubacterial DNA ligase by arylamino compounds. Antimicrob Agents Chemother. 1999;43:2766-72 pubmed
    ..The arylamino compounds appear to target eubacterial DNA ligase in vivo, since a Salmonella Lig(-) strain that has been rescued with the ATP-dependent T4 DNA ligase is less sensitive than the parental Salmonella ..
  8. Gumport R, Lehman I. Structure of the DNA ligase-adenylate intermediate: lysine (epsilon-amino)-linked adenosine monophosphoramidate. Proc Natl Acad Sci U S A. 1971;68:2559-63 pubmed
  9. Konrad E, Modrich P, Lehman I. Genetic and enzymatic characterization of a conditional lethal mutant of Escherichia coli K12 with a temperature-sensitive DNA ligase. J Mol Biol. 1973;77:519-29 pubmed
  10. Pascal J. DNA and RNA ligases: structural variations and shared mechanisms. Curr Opin Struct Biol. 2008;18:96-105 pubmed publisher
    ..Together with unliganded crystal structures of DNA and RNA ligases, a more comprehensive and dynamic understanding of the multi-step ligation reaction mechanism has emerged. ..
  11. Olivera B, Lehman I. Linkage of polynucleotides through phosphodiester bonds by an enzyme from Escherichia coli. Proc Natl Acad Sci U S A. 1967;57:1426-33 pubmed
  12. Gefter M, Becker A, Hurwitz J. The enzymatic repair of DNA. I. Formation of circular lambda-DNA. Proc Natl Acad Sci U S A. 1967;58:240-7 pubmed
  13. Modrich P, Lehman I. Enzymatic characterization of a mutant of Escherichia coli with an altered DNA ligase. Proc Natl Acad Sci U S A. 1971;68:1002-5 pubmed
    ..The mutant is killed by growth at 42 degrees C, a temperature at which it displays aberrant DNA synthesis. These results suggest that the ligase is necessary for normal DNA metabolism and viability in this strain. ..
  14. Billen D, Hellermann G, Stallions D. Role for deoxyribonucleic acid ligase in deoxyribonucleic acid polymerase i-dependent repair synthesis in toluene-treated escherichia coli. J Bacteriol. 1975;124:585-8 pubmed
    ..At the permissive temperature, 30 C, nearly normal semiconservative synthesis and limited repair synthesis were observed when DNA ligase was activated by the addition of nicotinamide adenine dinucleotide. ..
  15. Zhu H, Shuman S. Structure-guided mutational analysis of the nucleotidyltransferase domain of Escherichia coli NAD+-dependent DNA ligase (LigA). J Biol Chem. 2005;280:12137-44 pubmed
    NAD+-dependent DNA ligase (LigA) is essential for bacterial growth and a potential target for antimicrobial drug discovery...
  16. Filpula D, Fuchs J. Regulation of the synthesis of ribonucleoside diphosphate reductase in Escherichia coli: specific activity of the enzyme in relationship to perturbations of DNA replication. J Bacteriol. 1978;135:429-35 pubmed
    ..the nonpermissive temperature in Escherichia coli mutants temperature sensitive for DNA elongation (dnaE dnaG dnaZ lig) or DNA initiation (dnaA dnaC dnaI)...
  17. Kouzminova E, Kuzminov A. Chromosome demise in the wake of ligase-deficient replication. Mol Microbiol. 2012;84:1079-96 pubmed publisher
    ..The mechanism that converts unsealed nicks behind replication forks first into repairable double-strand breaks and then into irreparable double-strand gaps may be behind lethality of any DNA damaging treatment. ..
  18. Sadowski P. Suppression of a mutation in gene 3 of bacteriophage T7 (T7 endonuclease I) by mutations in phage and host polynucleotide ligase. J Virol. 1974;13:226-9 pubmed
    ..This is evidenced by a high plating efficiency and a large burst size compared to the single mutants. These findings may be explained by a limited destruction of cellular DNA by the double mutant. ..
  19. Amado L, Kuzminov A. Polyphosphate accumulation in Escherichia coli in response to defects in DNA metabolism. J Bacteriol. 2009;191:7410-6 pubmed publisher
    ..coli mutants with diverse defects in the DNA metabolism. We detected increased polyphosphate accumulation in the ligA, ligA recBCD, dut ung, and thyA mutants. Polyphosphate accumulation may thus be an indicator of general DNA stress.
  20. Karam J, Leach M, Heere L. Functional interactions beween the DNA ligase of Escherichia coli and components of the DNA metabolic apparatus of T4 bacteriophage. Genetics. 1979;91:177-89 pubmed
    ..coli lig gene) for growth. Viable E...
  21. Onda M, Yamaguchi J, Hanada K, Asami Y, Ikeda H. Role of DNA ligase in the illegitimate recombination that generates lambdabio-transducing phages in Escherichia coli. Genetics. 2001;158:29-39 pubmed
    ..A temperature-sensitive mutation in the lig gene reduced the frequency with which lambdabio-transducing phages were generated to 10-14% of that of wild type ..
  22. Wang L, Zhu H, Shuman S. Structure-guided Mutational Analysis of the Nucleotidyltransferase Domain of Escherichia coli DNA Ligase (LigA). J Biol Chem. 2009;284:8486-94 pubmed publisher
    NAD(+)-dependent DNA ligases (LigA) are ubiquitous in bacteria, where they are essential for growth and present attractive targets for antimicrobial drug discovery...
  23. Ivanchenko M, van Holde K, Zlatanova J. Prokaryotic DNA ligases unwind superhelical DNA. Biochem Biophys Res Commun. 1996;226:498-505 pubmed
    ..coli enzyme also unwound the DNA. Thus, prokaryotic DNA ligases can be added to an ever-growing list of DNA-binding proteins that unwind the DNA upon binding. ..
  24. Billen D, Hellermann G. Role of deoxyribonucleic acid polymerases and deoxyribonucleic acid ligase in x-ray-induced repair synthesis in toluene-treated Escherichia coli K-12. J Bacteriol. 1976;126:785-93 pubmed
    ..DNA polymerases II and III apparently cannot complete chain elongation and gap filling, and therefore repair carried out by these enzymes does not respond to ligase action. ..
  25. Morse L, Pauling C. Induction of error-prone repair as a consequence of DNA ligase deficiency in Escherichia coli. Proc Natl Acad Sci U S A. 1975;72:4645-9 pubmed
    ..coli. This mutator activity is unaffected by 3 mug/ml of chloramphenicol but is abolished both in lig-recA double mutants and by incubation with 20 mug/ml of chloramphenicol...
  26. Pauling C, Beck L. Role of DNA ligase in the repair of single strand breaks induced in DNA by mild heating of Escherichia coli. J Gen Microbiol. 1975;87:181-4 pubmed
  27. Konrad E, Modrich P, Lehman I. DNA synthesis in strains of Escherichia coli K12 with temperature-sensitive DNA ligase and DNA polymerase I. J Mol Biol. 1974;90:115-26 pubmed
  28. Uphoff S, Reyes Lamothe R, Garza de Leon F, Sherratt D, Kapanidis A. Single-molecule DNA repair in live bacteria. Proc Natl Acad Sci U S A. 2013;110:8063-8 pubmed publisher live Escherichia coli to directly visualize single fluorescent labeled DNA polymerase I (Pol) and ligase (Lig) molecules searching for DNA gaps and nicks, performing transient reactions, and releasing their products...
  29. Condra J, Pauling C. Induction of the SOS system by DNA ligase-deficient growth of Escherichia coli. J Gen Microbiol. 1982;128:613-21 pubmed
    ..These results indicate that ligase-deficient growth leads to the induction of the SOS system, and that all the above functions may respond to common induction signals. ..
  30. Heitman J, Ivanenko T, Kiss A. DNA nicks inflicted by restriction endonucleases are repaired by a RecA- and RecB-dependent pathway in Escherichia coli. Mol Microbiol. 1999;33:1141-51 pubmed
    ..These observations suggest that an increased number of DNA nicks can overwhelm the repair capacity of DNA ligase, resulting in the conversion of a proportion of DNA nicks into DNA lesions that require recombination for repair. ..
  31. Gottesman M, Hicks M, Gellert M. Genetics and function of DNA ligase in Escherichia coli. J Mol Biol. 1973;77:531-47 pubmed
  32. Cameron J, Panasenko S, Lehman I, Davis R. In vitro construction of bacteriophage lambda carrying segments of the Escherichia coli chromosome: selection of hybrids containing the gene for DNA ligase. Proc Natl Acad Sci U S A. 1975;72:3416-20 pubmed
    ..Two different hybrids were found with the same E. coli segment inserted in opposite orientations. Both hybrids produced similar levels of ligase as measured in crude extracts of infected cells. ..
  33. Munson B, Maier P, Greene R. Segregation of relaxed replicated dimers when DNA ligase and DNA polymerase I are limited during oriC-specific DNA replication. J Bacteriol. 1989;171:3803-9 pubmed
    ..The results also show that decatenation of dimers occurs readily on nicked dimer and represents an efficient pathway for processing replication intermediates in vitro. ..
  34. Feldberg R, Young H, Morrice L, Keir H. Some observations on the cofactor requirement for partially purified DNA ligase from Escherichia coli. FEBS Lett. 1972;27:345-9 pubmed
  35. Amado L, Kuzminov A. The replication intermediates in Escherichia coli are not the product of DNA processing or uracil excision. J Biol Chem. 2006;281:22635-46 pubmed
    ..These results are consistent with the previously proposed discontinuous replication of the leading strand in E. coli. ..
  36. Lopez de Saro F, O Donnell M. Interaction of the beta sliding clamp with MutS, ligase, and DNA polymerase I. Proc Natl Acad Sci U S A. 2001;98:8376-80 pubmed
  37. Horiuchi T, Sato T, Nagata T. DNA degradation in an amber mutant of Escherichia coli K12 affecting DNA ligase and viability. J Mol Biol. 1975;95:271-87 pubmed
  38. Pauling C, Hamm L. Properties of a DNA ligase mutant of Escherichia coli. II. Intermediates in DNA replication. Biochem Biophys Res Commun. 1969;37:1015-21 pubmed
  39. Barringer K, Orgel L, Wahl G, Gingeras T. Blunt-end and single-strand ligations by Escherichia coli ligase: influence on an in vitro amplification scheme. Gene. 1990;89:117-22 pubmed
  40. Wilkinson A, Smith A, Bullard D, Lavesa Curto M, Sayer H, Bonner A, et al. Analysis of ligation and DNA binding by Escherichia coli DNA ligase (LigA). Biochim Biophys Acta. 2005;1749:113-22 pubmed
    ..DNA ligases are essential enzymes in bacteria, with the most widely studied of this class of enzymes being LigA from Escherichia coli...
  41. Modrich P, Anraku Y, Lehman I. Deoxyribonucleic acid ligase. Isolation and physical characterization of the homogeneous enzyme from Escherichia coli. J Biol Chem. 1973;248:7495-501 pubmed
  42. Nandakumar J, Nair P, Shuman S. Last stop on the road to repair: structure of E. coli DNA ligase bound to nicked DNA-adenylate. Mol Cell. 2007;26:257-71 pubmed
    NAD(+)-dependent DNA ligases (LigA) are ubiquitous in bacteria and essential for growth...
  43. Panasenko S, Alazard R, Lehman I. A simple, three-step procedure for the large scale purification of DNA ligase from a hybrid lambda lysogen constructed in vitro. J Biol Chem. 1978;253:4590-2 pubmed
    ..Escherichia coli with a hybrid lambda prophage constructed in vitro that bears the ligase overproducing gene lop 11 lig+ (Panasenko, S., Cameron, J., Davis, R. W., and Lehman, I. R. (1977) Science 196, 188-189)...
  44. Tabor S. DNA ligases. Curr Protoc Mol Biol. 2001;Chapter 3:Unit3.14 pubmed publisher
    ..One is the source of energy: T4 ligase uses ATP, while E. coli ligase uses NAD. Another important difference is their ability to ligate blunt ends; under normal reaction conditions, only T4 DNA ligase will ligate blunt ends. ..
  45. Gottesman M. Isolation and characterization of a lambda specialized transducing phage for the Escherichia coli DNA ligase gene. Virology. 1976;72:33-44 pubmed
  46. Lavesa Curto M, Sayer H, Bullard D, Macdonald A, Wilkinson A, Smith A, et al. Characterization of a temperature-sensitive DNA ligase from Escherichia coli. Microbiology. 2004;150:4171-80 pubmed
    ..Compared to wild-type LigA, at 20 degrees C purified LigA251 has 20-fold lower ligation activity in vitro, and its activity is reduced further ..
  47. Georlette D, Blaise V, Dohmen C, Bouillenne F, Damien B, Depiereux E, et al. Cofactor binding modulates the conformational stabilities and unfolding patterns of NAD(+)-dependent DNA ligases from Escherichia coli and Thermus scotoductus. J Biol Chem. 2003;278:49945-53 pubmed
    ..Finally, guanidine hydrochloride-induced unfolding of NAD(+)-dependent DNA ligases is shown to be a complex process that involves accumulation of at least two equilibrium intermediates, the molten globule and its precursor. ..
  48. Chauleau M, Shuman S. Kinetic mechanism and fidelity of nick sealing by Escherichia coli NAD+-dependent DNA ligase (LigA). Nucleic Acids Res. 2016;44:2298-309 pubmed publisher
    Escherichia coli DNA ligase (EcoLigA) repairs 3'-OH/5'-PO4 nicks in duplex DNA via reaction of LigA with NAD(+) to form a covalent LigA-(lysyl-Nζ)-AMP intermediate (step 1); transfer of AMP to the nick 5'-PO4 to form an AppDNA ..
  49. Srivastava S, Tripathi R, Ramachandran R. NAD+-dependent DNA Ligase (Rv3014c) from Mycobacterium tuberculosis. Crystal structure of the adenylation domain and identification of novel inhibitors. J Biol Chem. 2005;280:30273-81 pubmed
    ..The results can be used as the basis for rational design of novel antibacterial agents. ..
  50. Sriskanda V, Schwer B, Ho C, Shuman S. Mutational analysis of Escherichia coli DNA ligase identifies amino acids required for nick-ligation in vitro and for in vivo complementation of the growth of yeast cells deleted for CDC9 and LIG4. Nucleic Acids Res. 1999;27:3953-63 pubmed
    ..coli ligase are defective in DNA repair. This suggests that the structural domains unique to yeast Cdc9p are not essential for mitotic growth, but may facilitate DNA repair. ..
  51. Kowalczykowski S, Dixon D, Eggleston A, Lauder S, Rehrauer W. Biochemistry of homologous recombination in Escherichia coli. Microbiol Rev. 1994;58:401-65 pubmed
    ..This review focuses on the biochemical mechanisms underlying these steps, with particular emphases on the activities of the proteins involved and on the integration of these activities into likely biochemical pathways for recombination. ..
  52. Ishino Y, Shinagawa H, Makino K, Tsunasawa S, Sakiyama F, Nakata A. Nucleotide sequence of the lig gene and primary structure of DNA ligase of Escherichia coli. Mol Gen Genet. 1986;204:1-7 pubmed
    ..We determined the nucleotide sequence of the lig gene of Escherichia coli coding for DNA ligase and flanking regions...
  53. Little J, Zimmerman S, Oshinsky C, Gellert M. Enzymatic joining of DNA strands, II. An enzyme-adenylate intermediate in the dpn-dependent DNA ligase reaction. Proc Natl Acad Sci U S A. 1967;58:2004-11 pubmed
  54. Sato T, Horiuchi T, Nagata T. Genetic analyses of an amber mutation in Escherichia coli K-12, affecting deoxyribonucleic acid ligase and viability. J Bacteriol. 1975;124:1089-96 pubmed
    Genetic analyses of an Escherichia coli K-12 mutant possessing the amber mutation lig-321 were carried out. This mutant is defective in deoxyribonucleic acid (DNA) ligase and conditionally lethal...
  55. Gellert M, Little J, Oshinsky C, Zimmerman S. Joining of DNA strands by DNA ligase of E. coli. Cold Spring Harb Symp Quant Biol. 1968;33:21-6 pubmed
  56. Ishino Y, Shinagawa H, Makino K, Amemura M, Nakata A. Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol. 1987;169:5429-33 pubmed
    ..Neither the isozyme-converting activity nor labeled Iap proteins were detected in the osmotic-shock fluid of cells carrying a multicopy iap plasmid. The Iap protein seems to be associated with the membrane. ..
  57. Bianco P, Tracy R, Kowalczykowski S. DNA strand exchange proteins: a biochemical and physical comparison. Front Biosci. 1998;3:D570-603 pubmed
    ..coli, UvsX protein from Bacteriophage T4, and RAD51 protein from Saccharomyces cerevisiae. ..
  58. Nagata T, Horiuchi T. An amber dna mutant of Escherichia coli K12 affecting DNA ligase. J Mol Biol. 1974;87:369-73 pubmed
  59. Brötz Oesterhelt H, Knezevic I, Bartel S, Lampe T, Warnecke Eberz U, Ziegelbauer K, et al. Specific and potent inhibition of NAD+-dependent DNA ligase by pyridochromanones. J Biol Chem. 2003;278:39435-42 pubmed
  60. Liebart J, Paolozzi L, Camera M, Pedrini A, Ghelardini P. The expression of the DNA ligase gene of Escherichia coli is stimulated by relaxation of chromosomal supercoiling. Mol Microbiol. 1989;3:269-73 pubmed
    ..The level of suppression correlates with the degree of DNA relaxation observed, suggesting that the gene encoding the E. coli DNA ligase is activated by relaxation of the chromosomal DNA. ..
  61. Lehman I. DNA ligase: structure, mechanism, and function. Science. 1974;186:790-7 pubmed
    ..coli chromosome. DNA ligase is therefore an essential enzyme required for normal DNA replication and repair in E. coli. Purified DNA ligases have proved to be useful reagents in the construction in vitro of recombinant DNA molecules. ..
  62. Panasenko S, Modrich P, Lehman I. Modification of Escherichia coli DNA ligase by cleavage with trypsin. J Biol Chem. 1976;251:3432-5 pubmed
    ..These findings demonstrate that portions of the DNA ligase molecule that are required for phosphodiester bond formation are not required for at least one of the partial reactions catalyzed by this enzyme. ..